title: NF-κB activation in myeloid cells mediates ventilator-induced lung injury.
abstract: BACKGROUND
  Although use of the mechanical ventilator is a life-saving intervention, excessive tidal volumes will activate NF-κB in the lung with subsequent induction of lung edema formation, neutrophil infiltration and proinflammatory cytokine/chemokine release. The roles of NF-κB and IL-6 in ventilator-induced lung injury (VILI) remain widely debated.
  
  
  METHODS
  To study the molecular mechanisms of the pathogenesis of VILI, mice with a deletion of IкB kinase in the myeloid cells (IKKβ(Δmye)), IL-6(-/-) to WT chimeric mice, and C57BL/6 mice (WT) were placed on a ventilator for 6 hr.WT mice were also given an IL-6-blocking antibody to examine the role of IL-6 in VILI.
  
  
  RESULTS
  Our results revealed that high tidal volume ventilation induced pulmonary capillary permeability, neutrophil sequestration, macrophage drifting as well as increased protein in bronchoalveolar lavage fluid (BALF). IL-6 production and IL-1β, CXCR2, and MIP2 expression were also increased in WT lungs but not in those pretreated with IL-6-blocking antibodies. Further, ventilator-induced protein concentrations and total cells in BALF, as well as lung permeability, were all significantly decreased in IKKβ(Δmye) mice as well as in IL6(-/-) to WT chimeric mice.
  
  
  CONCLUSIONS
  Given that IKKβ(Δmye) mice demonstrated a significant decrease in ventilator-induced IL-6 production, we conclude that NF-κB-IL-6 signaling pathways induce inflammation, contributing to VILI, and IкB kinase in the myeloid cells mediates ventilator-induced IL-6 production, inflammation, and lung injury.
authors.affiliation: Department of Biological Sciences, National Sun Yat-Sen University, Kaohsiung 804, Taiwan.
authors.forename: Yi-An
authors.initials: YA
authors.lastname: Ko
authors.forename: Ming-Chieh
authors.initials: MC
authors.lastname: Yang
authors.forename: Hung-Tu
authors.initials: HT
authors.lastname: Huang
authors.forename: Ching-Mei
authors.initials: CM
authors.lastname: Hsu
authors.forename: Lee-Wei
authors.initials: LW
authors.lastname: Chen
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology*; D002478:Cells, Cultured; D015850:Interleukin-6 / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D022423:Myeloid Cells / Q000276:immunology* / Q000473:pathology; D016328:NF-kappa B / Q000276:immunology*; D055397:Ventilator-Induced Lung Injury / Q000276:immunology* / Q000473:pathology*
chemical_list: D015850:Interleukin-6; D016328:NF-kappa B; C577686:interleukin-6, mouse